The capsule of Porphyromonas gingivalis reduces the immune response of human gingival fibroblasts

To examine the role of the CPS in host-pathogen interactions we constructed an insertional isogenic P. gingivalis knockout in the epimerase-coding gene epsC that is located at the end of the CPS biosynthesis locus. This mutant was subsequently shown to be non-encapsulated. K1 capsule biosynthesis could be restored by in trans expression of an intact epsC gene. We used the epsC mutant, the W83 wild type strain and the complemented mutant to challenge human gingival fibroblasts to examine the immune response by quantification of IL-1β, IL-6 and IL-8 transcription levels. For each of the cytokines significantly higher expression levels were found when fibroblasts were challenged with the epsC mutant compared to those challenged with the W83 wild type, ranging from two times higher for IL-1β to five times higher for IL-8.These experiments provide the first evidence that P. gingivalis CPS acts as an interface between the pathogen and the host that may reduce the host's pro-inflammatory immune response. The higher virulence of encapsulated strains may be caused by this phenomenon which enables the bacteria to evade the immune system.Porphyromonas gingivalis is a major pathogen in destructive periodontal diseases including chronic and aggressive periodontitis that are characterized by breakdown of the tooth-supporting tissues [1-3]. P. gingivalis is a black pigmented, often encapsulated, strict anaerobic, Gram negative coccobacillus that occurs in the human oral cavity.Among the variety of virulence factors that have been described for P. gingivalis, CPS has shown to be a major factor in experimental infections. Studies in a mouse infection model have revealed that encapsulated P. gingivalis strains are more virulent than non-encapsulated strains [4-7]. Non-encapsulated strains mostly cause non-invasive, localized abscesses whereas encapsulated strains cause invasive, spreading phlegmonous infections after subcutaneous inoculation of experimental animals.Six distinct capsu